tbuckley/cabot-search huggingface dataset:
Integrating the 31-gene expression profile test into clinical decision-making to guide risk-aligned care decisions for patients with stage I-III cutaneous melanoma: NCI-SEER Analysis.
Authors: David Hyams, Valentina I. Petkov, Jung S. Byun, Brian Martin, Christine N. Bailey, Brian Gastman
Journal: Journal of Clinical Oncology (2023)

6601 Background: Cutaneous melanoma (CM) management depends on an estimate of recurrence risk or death. Because of recognized disease risk and drug efficacy, pembrolizumab immunotherapy has been approved for stage IIB-C patients. However, it is a treatment with potential financial and biological toxicities with 16% of patients experiencing severe treatment related adverse events. Improved risk stratification could identify individuals for whom more selective management would be appropriate. In collaboration with the NCI Surveillance, Epidemiology, and End Results (SEER) program, which includes information on patients tested with a 31-gene expression profile (31-GEP) test in an unbiased and unselected manner, we confirm the 31-GEP adds independent prognostic value in patients with stage I-III CM, and investigated whether the 31-GEP could identify stage IIB-C patients who might reasonably avoid adjuvant therapy while also identifying patients with stage I disease who might benefit from more aggressive diagnostic and/or therapeutic intervention. Methods: SEER registries linked CM cases diagnosed 2013-2018 to 31-GEP test results provided by Castle Biosciences (9,207 matched) using a registry trusted third party (honest broker), including subsets of stage IIB-IIC (n=775) and stage I (n=5,651) melanoma. The primary endpoint was melanoma-specific survival (MSS). The 31-GEP risk-groups included Class 1A (low), Classes 1B/2A (intermediate), and Class 2B (high). Each was compared using Kaplan-Meier analysis and the log-rank test. Results: In the overall cohort, patients with a Class 1A result had a significantly higher 5-year MSS than a Class 1B/2A or Class 2B result (97.4% vs. 93.5% vs. 83.3%, p&lt;0.001). In multivariable analysis, a Class 2B result (HR=3.26, p&lt;0.001) and positive lymph node status (HR=3.41, p&lt;0.001) were the strongest predictors of diminished MSS. In stage IIB-C, 18.8% (146/775) of patients received a Class 1A result with an associated 5-year MSS of 89.1% (vs. Class 2B: 76.6%, p=0.001), despite the absence of pembrolizumab approval for the evaluated SEER population. Alternatively, 4.6% (260/5,651) of patients with stage I disease had a Class 2B result, with an associated 5-year MSS of 92.3% (vs. Class 1A: 98.0%, p&lt;0.001). Conclusions: The SEER database allowed a non-biased analysis of a large cohort of patients with stage I-III CM who were tested with the 31-GEP. The 31-GEP identifies patients, including those with stage IIB-C disease, with favorable outcomes and could help physicians and patients decide whether to pursue adjuvant therapy. Moreover, the 31-GEP identities high-risk patients, including those with stage I disease, for whom more aggressive follow-up and early intervention should be considered.
Gilteritinib plus azacitidine and venetoclax for FLT3-ITD mutated relapsed/refractory acute myeloid leukemia.
Authors: Nianci Chen, Yile Zhou, Hongyan Tong, Juying Wei, YinJun Lou, De Zhou, Cuihua Fan, Li Huang, Liping Mao, Chenying Li, Huafeng Wang, Jie Jin
Journal: Journal of Clinical Oncology (2023)

e19024 Background: Gilteritinib is a second-generation FLT3 tyrosine kinase inhibitor that has been shown significantly increase the survival of relapsed/refractory (r/r) FLT3-mutated acute myeloid leukemia (AML) patients. We investigated the clinical benefit of gilteritinib plus azacitidine and venetoclax in the treatment of r/r FLT3-ITD mutated AML in the real word. Methods: Gilteritinib was given by oral administration at a dose of 80 or 120mg/d for each cycle. Azacitidine was intravenously administrated at a dose of 75 mg/m 2 /day d1-7. Venetoclax was given by oral administration at a dose of 100mg/d then ramp-up at 400mg/d, some patients were administrated at a dose of 400mg/d due to prior exposure. The composite complete response (CRc) rate (complete response [CR] and CR with incomplete blood count recovery [CRi]) were assessed, and then the overall survival (OS), event-free survival (EFS), relapse-free survival (RFS) was evaluated. Results: We retrospectively analyzed the outcomes of gilteritinib plus azacitidine and venetoclax in 14 r/r FLT3-ITD mutated AML patients. The CRc rate of the triple therapy was 57.1% (CR, n = 5, 35.7%; CRi, n = 3, 21.4%), in which, all patients achieved minimal residual disease (MRD) negative measured by multi-color flow cytometry. At a median follow-up of 136.5 days, the median OS was 216.0 days, the median EFS was 97.0 days, and the median RFS were 184 days. The common grade 3/4 hematologic adverse events included neutropenia (n = 14, 100.0%), anemia (n = 12, 85.7%), and thrombocytopenia (n = 11, 78.6%). The common grade 3/4 non-hematologic adverse events were pulmonary infection (n = 5, 35.7%), other adverse events were relatively less and milder. Conclusions: In conclusion, the current data demonstrated promising response of the triple therapy in r/r FLT3-ITD mutated AML patients, and the regimen represented a potential option as a bridge to transplant. Prospective studies are warranted to further define the risk or benefit for more patients.
Biosimilar uptake and cost savings analysis before and after implementation of a pharmacist-driven substitution program within a National Community Oncology Network: One-year follow-up.
Authors: Melody Chang, Jenny Li, Brooke Peters, Bradley Winegar, Robert Carr, Camilo Rodriguez, Ashley Kohler-Gerber, Darell Connor, Taqyra Freeman, Kyle Brown
Journal: Journal of Clinical Oncology (2023)

6516 Background: As of December 2022, 22 of the 40 biosimilar approvals in the United States, are used for the treatment of cancer or for the supportive care of patients with cancer. Our organization is a network of community oncology practices, representing 107 oncologists at 76 locations across 17 states. Because our network faces formulary selection and reimbursement challenges related to a diverse payor mix across multiple states, we sought to see the impact of utilizing regional clinical pharmacists (RCPs) to assist with selection of the most cost-effective biosimilar products. Methods: In October 2021, our network initiated an RCP-driven biosimilar substitution program, whereby the RCP acts as a liaison between providers and financial teams to evaluate existing drug orders and their financial impact. We previously presented data on the financial impact to payors and providers before and after implementation of the program from 4/1/2021 to 4/1/2022. This study evaluates the one-year results following program implementation. Additionally, outcomes related to biosimilar utilization as well as financial impacts to payors, patients, and providers were assessed. Payor savings is defined as the difference of the calculated 80% Medicare ASP+6 for the administered biosimilar compared to the originator; patient savings is defined as the difference of the calculated 20% Medicare ASP+6 co-insurance for the administered biosimilar compared to the originator; provider savings is defined as the difference between the invoiced cost of the biosimilar compared to the originator. Results: By the end of 2022, preferred product utilization was achieved for &gt;90% of bevacizumab, trastuzumab, and rituximab orders. Use of the preferred pegfilgrastim product increased from &lt;20% in 4/2021 to &gt;60% by 12/2022. Use of filgrastim biosimilar product increased from &lt;75% in 4/2021 to &gt;90% by 4/2022, then decreased to 55% by 12/2022 due to trending ASP. Payor preference prevented biosimilar switching in approximately 34% of cases. Conclusions: Use of institution-preferred biosimilar products increased across all agents in this study after implementation of the RCP-driven biosimilar substitution program, except for filgrastim. Significant cost savings were noted for payors, patients, and providers. Barriers to switching to institution-preferred products included non-medical switching requirements by payors, patient assistance and compassionate use programs, and patient and/or provider preferences. [Table: see text]
The genetics of transformation from myelodysplastic syndrome to secondary acute myeloid leukemia.
Authors: Zhenyu Zhang, Hong Zhang, Yani Lin, Miaoqing Zhao, Kun Ru
Journal: Journal of Clinical Oncology (2023)

e19073 Background: Gene mutations play key role in the transformation from myelodysplastic syndrome (MDS) to secondary acute myeloid leukemia (s-AML). The aim of this study was to explore the clonal progression pattern from MDS to s-AML. Methods: A total of 663 patients diagnosed with MDS (n = 291), s-AML (n = 86), and primary AML (p-AML) (n = 286, M3 excluded) were enrolled in this study from May 2018 to December 2021, and the median age was 57 year-old (range 1~88). The diagnosis was established according to the WHO criteria. The MDS patients were divided into low-risk MDS ( n = 158) and high-risk MDS (n = 133) according to 2012 IPSS-R. Next generation sequencing was performed to detect the mutations of entire coding regions of 112 genes related with hematologic tumors in all patients. Results: It was found that mutations from 31 genes occurred in both MDS and AML, including DNA methylation ( DNMT3A, TET2, IDH1, IDH2, WT1), chromatin modification ( SETBP1, ASXL1, EZH2, PHF6), RNA splicing ( U2AF1, SF3B1, SRSF2, ZRSR2), transcription regulation ( TP53, CEBPA, RUNX1, ETV6, GATA2, BCOR, BCORL1), signal transduction pathways ( NRAS, KRAS, PTPN11, NOTCH1, FLT3, JAK2, KIT), and others ( NPM1, FAT, STAG2, DDX41). By enrichment analysis, those mutations were classified into two categories: type A mutations ( FLT3, IDH1, NPM1, NRAS, PTPN11, WT1, CEBPA) and type B mutations ( IDH2, KRAS, U2AF1, ZRSR2, SRSF2, STAG2, DNMT3A, EZH2, RUNX1, ETV6, TP53). The type A genes were significantly enriched in p-AML than in MDS, while some type B mutations, particularly RNA splicing, were significantly enriched in MDS than in p-AML. The VAFs of type A mutations were significantly lower than those of type B mutations. The longitudinal analysis of 10 patients with s-AML revealed two main models of clonal evolution, linear evolution and clone sweeping. Although the two models differed in the disease development, new sub-clones appeared in 9/10 patients. Interestingly, many of the new mutations were type A mutations (n = 7, 7/10), and 7 out of 10 patients carried type B mutations when they were at MDS state. The VAF data also showed that the preexisting mutations were generally higher than the newly emerging genetic alterations. Finally, an individual case was used to delineate the clone evolution. The patient was initially diagnosed with 5q syndrome and U2AF1 mutation (type B) was identified. After treatment, the patient experienced remission, and developed a new ETV6 mutation while the clonal size of U2AF1 decreased. When the patient relapsed, the clone size of ETV6 decreased while U2AF1 mutated clone size were amplified, a typical “clone sweeping” pattern. When the patient eventually transformed to s-AML, three type A mutations ( NRAS, KRAS and PTPN11) appeared simultaneously. Conclusions: This study revealed that the type A mutations are mainly responsible for the progression of MDS to AML, and the type B mutations are related to the clonal origin of MDS.
A single institution experience of multimodality radiation therapy for muscle-invasive bladder cancer.
Authors: Monica Nair, Jessica Scarborough, Shilpa Gupta, Timothy D. Gilligan, Amanda Nizam, Moshe Chaim Ornstein, Jessica Echle, Jay P. Ciezki, Kevin L. Stephans, Rahul D. Tendulkar, Jacob Scott, Omar Y. Mian
Journal: Journal of Clinical Oncology (2023)

e16614 Background: We studied a cohort of patients with localized muscle invasive bladder cancer (MIBC) who received organ preserving trimodality therapy (TMT) as definitive treatment at a single high-volume institution. Methods: A retrospective cohort analysis was performed for 231 bladder cancer patients treated with definitive radiation or chemoradiation therapy from 2006 to 2022 at a single institution. We assessed overall and disease-free survival as defined by any type of cancer recurrence. We analyzed survival outcomes based on stage, pathologic features, and patient characteristics. Results: 184 of 231 patients in this cohort received either definitive radiation therapy alone or with chemoradiation and had adequate follow-up data for analysis. The median overall survival for these 184 patients was 37mo (95%CI 28-67). Disease free survival (DFS) had a median time of 36mo (95% CI 23-69). On univariate analysis neither tumor size nor hydronephrosis showed a significant association with local recurrence. The presence of carcinoma in situ (CIS) was associated with shorter time to local recurrence (Log-Rank p = 0.039). Nine patients (4.9%) required cystectomy after initial definitive radiation therapy. When overall survival was compared between patients offered radical cystectomy who proceeded with definitive multimodal radiation therapy and radical cystectomy ineligible patients, there was a significantly longer overall survival for the cystectomy eligible patients (median 86mo (95%CI 35-206) vs median 31mo (95%CI 24-44), Log-Rank p = 0.0016). No differences were observed in cancer specific survival between cystectomy eligible and ineligible patients. Conclusions: Multimodality bladder preservation demonstrated cancer specific survival outcomes comparable to published radical cystectomy series. The presence of CIS at baseline was associated with increased local recurrence, but not CSS or OS. Eligibility for radical cystectomy was associated with longer overall survival in patients treated with TMT, highlighting the limitations of retrospective comparisons of all-cause mortality between different treatment approaches. Disease specific survival endpoints, propensity matching analyses, or randomized prospective trials are needed to draw comparative efficacy conclusions.
Impact of COVID-19 pandemic on breast cancer screening rates.
Authors: Cliff Rutter, Elisea Avalos-Reyes, Rogelio A. Brito, Kelly Craig, Dorothea J. Verbrugge, Chen Liu, Emily Kipping, Kjel Andrew Johnson
Journal: Journal of Clinical Oncology (2023)

e18875 Background: The COVID-19 pandemic disrupted healthcare utilization in the US, with cancer screening being severely impacted. Little is known about the impact COVID-19 had nationally on breast cancer screening. The objective of this study was to examine the potential impact of the COVID-19 pandemic on breast cancer screening rates. Methods: Commercial Fully Insured and Medicare members of large national health plan meeting the Healthcare Effectiveness Data and Information Set (HEDIS) inclusion and exclusion criteria for the measurement years 2019, 2020 and 2021 were included in the study. Member demographic data were linked to race, zip code, socioeconomic status and region information. The pre-COVID period was defined as measurement year 2019, peak-COVID was defined as measurement year 2020 and post-peak-COVID-19 was defined as measurement year 2021. Screening incidence rate differences (IRD) and ratios (IRR) were calculated between the three time periods. Logistic regression was conducted to control for socio-demographic confounders. All analyses were conducted in Python; a p-value less than 0.05 was significant. Results: This study included 324,707, 400,740 and 532,879 members in pre-COVID, peak-COVID and post-peak-COVID periods, respectively. The screening IRD between pre-COVID and peak-COVID periods was -3.1% (95% confidence interval [CI] -3.5% to -2.7%; p &lt; 0.001) and the IRR was 0.961 (95% CI 0.956 – 0.966; p &lt; 0.001). Between the peak-COVID and post-peak-COVID periods, the IRD was -0.33% (95% CI -0.68% to 0.02%; p = 0.0675) and the IRR was 0.996 (95% CI 0.991-1.000; p = 0.0667). Comparing the pre-COVID to the post-peak-COVID period revealed a significant IRD (-3.4% [95% CI -3.8% to -3.0%]; p &lt; 0.0001) and IRR (0.956 [95%CI 0.952-0.961]; p &lt; 0.0001). Controlling for other confounders, the pre-COVID period was associated with significantly higher odds of receiving a screening mammogram compared to the peak-COVID period (odds ratio [OR]: 1.19 [95% CI 1.17-1.2], p &lt; 0.0001). Additionally, the post-peak-COVID period was associated with lower odds compared to the peak-COVID period (OR: 0.98 [95% CI 0.97-0.99], p &lt; 0.0001). Additional results are shown in Table 1. Conclusions: The COVID-19 pandemic resulted in significantly lower screening mammogram rates when compared to the pre-COVID period. Additionally, this decrease appeared to be durable into the post-peak-COVID period after controlling for other confounders for screening. Further follow up studies are warranted to characterize the potential rebound of screenings. [Table: see text]
Evaluation of cardiac failure and recovery in acute myelogenous leukemia.
Authors: Matthew Wu, Katie Russell, Carole Shaw, Anna B. Halpern, Cristina Maria Ghiuzeli, Jacob Appelbaum, Paul Hendrie, Roland B. Walter, Mary-Elizabeth M. Percival
Journal: Journal of Clinical Oncology (2023)

7038 Background: Cardiac failure causes significant comorbidity and death in acute myeloid leukemia (AML) patients, with incidence estimated at 10-15% (Neuendorff N Blood Adv. 2020). We sought to describe the post-treatment cardiac experience in AML survivors including factors associated with onset, persistence, and outcome of cardiac dysfunction during and following treatment. Methods: 86 patients with AML or other high-grade myeloid neoplasms treated with induction chemotherapy with or without allogeneic hematopoietic cell transplant were identified at the University of Washington/Fred Hutchinson Cancer Center from 1/2000-1/2022. All patients sustained cardiac dysfunction, defined as left ventricular ejection function (LVEF) decline of 10% with absolute LVEF below 50% during chemotherapy. A multivariable analysis was performed to compare those who recovered (LVEF recovery) and those who did not (LVEF non-recovery), examining baseline health factors, disease risk (ELN 2017), time to dysfunction and recovery, most probable cause of cardiac dysfunction based on cardiologist evaluation, and goal-directed medical therapy (GDMT) use and dosage. Results: 48% (41 out of 86) failed to recover following LVEF decline. This cohort tended to be older, male, and had more ASCVD risk factors ( p &lt; 0.05). Neither the choice of chemotherapy regimen ( p= 0.43) nor the cumulative anthracycline dose ( p= 0.44) was significantly different between the LVEF recovery and non-recovery groups. Onset of cardiac dysfunction tended to occur later in the LVEF recovery cohort (median 72 vs. 48.5 days, p= 0.660). In subjects who recovered, the median time to recovery was 87 days (range 2-268 days). When chemotherapy was identified as the probable cause, it was associated with greater likelihood of eventual recovery ( p= 0.014), whereas ischemic coronary etiology was associated with non-recovery ( p= 0.005). Failing to recover from cardiac dysfunction correlated with shorter survival (median 229 vs 650 days, p = 0.005). Multivariable analysis is shown in the Table below. Importantly, the use of GDMT with higher doses of renin-angiotensin inhibitor medications (RAASi) were associated with higher probability of recovery (not shown, p &lt; 0.05). Conclusions: The present study demonstrates recovery occurring in over half of AML patients who experienced cardiac dysfunction during their chemotherapy. Recovery was more common in patients whose cardiac dysfunction is precipitated by chemotherapy and in patients who received GDMT with aggressive use of RAASi. Since cardiac recovery was associated with improved survival, next steps include establishing a cardiac monitoring algorithm to initiate early and aggressive GDMT. [Table: see text]
Real-world experience and outcomes of immune-checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC).
Authors: Samuel Paul, Eric Min, Katherine K Benson, Menglin Xu, Anne M. Noonan, Arjun Mittra, Pannaga G. Malalur, Sameek Roychowdhury, Ning Jin, John L. Hays, Rifat T. Elkhatib, Shafia Rahman, Eric David Miller, Dayssy Alexandra Diaz Pardo, Ashish Manne
Journal: Journal of Clinical Oncology (2023)

e16155 Background: Effective management of HCC needs concerted efforts of all the disciplines involved. ICI and its combinations have not improved the outcomes to the expected level outside clinical trials. This is a retrospective review of HCC patients treated with ICI in an academic institution. Methods: HCC patients who received at least one ICI dose between 1/1/2017 and 7/31/2021 at the Ohio State University were included in the study. The patient's baseline (BL) characteristics (at the first dose of ICI) were extracted with immune-related adverse events (irAE) details and survival outcomes. Descriptive statistics were used, Fisher exact test to compare categorical variables, log-rank test rank test for survival outcomes, and logistic regression model for categorical outcomes using JMP Pro 16 (SAS Institute Inc., Cary, NC). Results: Our cohort has 38 patients. The median age is 67 years (range 41-88), with 82% males and 90% Caucasians (7% African American and 3% other). Refer to the table for other BL characteristics. Median overall survival (OS) and progression-free survival were 6 months (m) (95% confidence interval [CI], 4-10) and 4m (95% CI, 3-6), respectively. The OS was better in patients with longer DoT (≤ 2m vs 3-6m vs ≥6m, 2m vs 5m vs 24m, p&lt;0.001). Even though PFS was significantly better in patients with CP A-B9 (Vs B9-C, 6m vs 2.5m, p=0.03) and CP B (vs A vs C, 9m vs 5m vs 2m, p=0.02), OS was not different. Poor responders (&lt;2 m vs ≥ 3m PFS) in this cohort had higher BL total bilirubin (TB) (p=0.03) and are more likely to have CPC (p=0.03) or CP B9-C (p=0.01) and BCLC D (p=0.04) patients. CP class (lower, p=0.0007), DoT (≥ 6m, p=0.0001), combination with bev (p=0.004), fewer liver lesions (≤2, &lt; 0.001), no history of any LRT (p=0.01) or fewer LRTs (p=0.01), and non-metastatic disease (p&lt; 0.001) are associated with better OS. PVTT, line of therapy, and ALBI G did not impact the OS. IrAE were reported just 4 (10%) patients. Conclusions: In this small retrospective cohort, lower volume of hepatic HCC lesions, use of ICI with bev, lower TB, longer DoT were associated with better OS, while more advanced disease, CPC, BCLC D, more LRTs and higher bilirubin resulted in worse survival. Our results suggest that prescribing ICI in line with FDA approval indications results in better outcomes. They must be validated in larger studies. [Table: see text]